Melioidosis is a severe and fatal infectious disease in the tropics and subtropics. It presents as a febrile illness with protean manifestation ranging from chronic localized infection to acute fulminant septicemia with dissemination of infection to multiple organs characterized by abscesses. Pneumonia is the most common clinical presentation. Because of the wide range of clinical presentations, physicians may often misdiagnose and mistreat the disease for tuberculosis, pneumonia or other pyogenic infections. The purpose of this paper is to present common pitfalls in diagnosis and provide optimal approaches to enable early diagnosis and prompt treatment of melidoidosis. Melioidosis may occur beyond the boundaries of endemic areas. There is no pathognomonic feature specific to a diagnosis of melioidosis. In endemic areas, physicians need to expand the diagnostic work-up to include melioidosis when confronted with clinical scenarios of pyrexia of unknown origin, progressive pneumonia or sepsis. Radiological imaging is an integral part of the diagnostic workup. Knowledge of the modes of transmission and risk factors will add support in clinically suspected cases to initiate therapy. In situations of clinically highly probable or possible cases where laboratory bacteriological confirmation is not possible, applying evidence-based criteria and empirical treatment with antimicrobials is recommended. It is of prime importance that patients undergo the full course of antimicrobial therapy to avoid relapse and recurrence. Early diagnosis and appropriate management is crucial in reducing serious complications leading to high mortality, and in preventing recurrences of the disease. Thus, there is a crucial need for promoting awareness among physicians at all levels and for improved diagnostic microbiology services. Further, the need for making the disease notifiable and/or initiating melioidosis registries in endemic countries appears to be compelling. Melioidosis is a severe and fatal infectious disease in the tropics and subtropics. It presents as a febrile illness with protean manifestation ranging from chronic localized infection to acute fulminant septicemia with dissemination of infection to multiple organs characterized by abscesses. Pneumonia is the most common clinical presentation Because of the wide range of clinical presentations, physicians may often misdiagnose and mistreat the disease for tuberculosis, pneumonia or other pyogenic infections. The purpose of this paper is to present common pitfalls in diagnosis and provide optimal approaches to enable early diagnosis and prompt treatment There is no pathognomonic feature specific to a diagnosis of melioidosis. In endemic areas, physicians need to expand the diagnostic work-up to include melioidosis when confronted with clinical scenarios of pyrexia of unknown origin, progressive pneumonia or Sepsis. Radiological imaging is an integral part of the diagnostic workup. Knowledge of the modes of transmission and risk factors will add support in clinically marked probabilities or possible cases. Where the laboratory bacteriological confirmation is not possible, applying evidence-based criteria and empirical treatment with antimicrobials is recommended. It is of prime importance that patients undergo the full course of antimicrobial therapy to avoid relapse and recurrence. Early diagnosis and appropriate management is crucial in reducing serious complications leading to high mortality, and Thus, there is a crucial need for promoting awareness among physicians at all levels and for improved diagnostic microbiology services. Further, the need for making the disease notifiable and / or initiating melioidosis registries in endemic countries appears to be compelling.